Children with the rare liver disorder PFIC face the possibility of cirrhosis and liver failure before their 10th birthday. Along the way, the disease manifests as severe itching without an FDA-approved therapeutic treatment. Until this week.
The regulator on Tuesday odevixibat approved, an Albireo Pharma drug developed to treat severe itching, or pruritus, in patients who have the liver disorder progressive familial intrahepatic cholestasis (PFIC). The decision was made a day after European regulators gave assent to the drug. Albireo, based in Boston, said the drug will be available in the United States in the next few days and will be marketed under the name “Bylvay.”
PFIC is an inherited liver disorder in which the organ cannot properly drain bile, leading to the accumulation of digestive fluid. The disease is classified into different subtypes, based on the genetic mutation. The only treatments for the condition were surgeries that diverted bile or a liver transplant. In a conference call Wednesday, Albireo CEO Ron Cooper said that interhepatic cholestasis was first described in the mid-1900s and that specific genes for PFIC were characterized in 1998. Approval of the Albireo drug FDA, in patients 3 months of age or older, covers all subtypes of PFIC.
“It took more than 20 years to make the impossible possible,” Cooper said. “We are now providing the first non-surgical treatment for PFIC patients and their families.”
According to Albireo, of the estimated 100,000 patients who have cholestatic liver disease, about 15,000 have PFIC, not counting those from China and India. The company estimates that there are about 600 patients with PFIC in the US How pruritus develops in patients with PFIC is not fully understood. The drug Albireo is a small molecule that decreases the reabsorption of bile acids. Manufactured as a capsule, the medicine can be swallowed in that form or sprinkled on soft food.
The FDA approval is based on data from two phase 3 clinical trials. In the first, a randomized, double-blind, placebo-controlled study, the drug met the primary goal of showing a statistically significant change in pruritus and symptoms. bile acids over the course of 72 weeks of treatment. Those results were confirmed in an open-label, phase 3 extension study, where the drug continued to show a sustained reduction in bile acids in the blood, as well as an improvement in itching for up to 48 weeks. The drug was well tolerated by the patients; the most common adverse reactions included elevated liver enzymes and diarrhea.
Itching has been shown to be a difficult target for drug developers. A small molecule developed by Menlo Therapeutics failed clinical trial testing in pruritus of unknown origin and pruritus associated with atopic dermatitis. The Bridgewater, NJ-based company, which was renamed VYNE Therapeutics, stopped compound development last year. Earlier this year, Stamford, Connecticut-based Cara Therapeutics reported on its experimental treatment for itching in mild to severe atopic dermatitis. failed a phase 2 study.
Among those seeking treatments for itching associated with liver and kidney conditions is Escient Pharmaceuticals of San Diego, backed by venture companies. Last week, the company reported the results of phase 1 demonstrating that its small molecule, EP547, was safe and well tolerated both by healthy volunteers and by patients with chronic kidney or liver disease.
Bylvay is dosed by weight, said Pamela Stephenson, Albireo’s chief commercial officer. The average weight of patients in clinical studies was 18 kilograms (approximately 39.6 pounds). At an average weight of 18kg, Bylvay’s annual average price, before any rebates or discounts, will be $ 385,000. The drug will be available in vials, each with a 30-day supply. Stephenson said the price per bottle will be released later.
With Bylvay’s approval, Albireo also received a rare disease priority review voucher. These vouchers entitle a company to receive a faster priority review of a future drug candidate. But companies can also sell these vouchers for prices in excess of $ 100 million. Chief Financial Officer Simon Harford said the company plans to sell its priority review coupon, but the timing of the sale and the price will depend on the market and how many companies want to buy the coupon.
Albireo reported having a cash position of $ 186.3 million at the end of June. Excluding any proceeds from the priority review voucher sale, the company estimates that its cash will support the company in 2023.
Albireo is also studying Bylvay in other rare liver diseases that affect children. Two phase 3 studies are ongoing, one in biliary atresia and the other in Alagille syndrome.
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